Model-Based Analysis Of The Relationship Between Pembrolizumab (Mk-3475) Exposure And Efficacy In Patients With Advanced Or Metastatic Melanoma.

3068 Background: Optimization of antibody dosing in oncology drug development is an area of growing interest. We have previously demonstrated that the dose and schedule of pembrolizumab does not correlate with clinical outcomes in melanoma. Here, we assess the relationship between steady state plasma exposure and tumor growth dynamics in patients enrolled in the KEYNOTE-001 and KEYNOTE-002 studies. Methods: Patients received pembrolizumab 2 mg/kg every 3 weeks (Q3W) to 10 mg/kg Q2W or Q3W. Exposure was defined as the area under the serum concentration curve (AUC) over 6 weeks. Response was defined as the change in tumor size per standard rules for measuring target lesions (ie, sum of the longest diameters). We assessed the extent of tumor growth and its reduction under pembrolizumab treatment using nonlinear mixed effects modeling; specifically, we tested whether individual exposures predict patterns of tumor response. Results: In this initial analysis, we found that reduction in tumor growth was best cha...